维吾尔族霍奇金淋巴瘤与HLA-DPA1、DPB1基因多态性的相关性分析

摘 要：［目的］ 研究人类白细胞抗原（human leukocyte antigen,HLA）DPA1、DPB1基因多态性与维吾尔族霍奇金淋巴瘤（Hodgkin’s lymphoma,HL）遗传易感性的关系。［方法］ 采用DNA直接测序分型（sequence based typing,SBT）法,检测40例维吾尔族HL患者和80名健康体检者的DPA1、DPB1基因多态性,对两组间的HLA-DPA1、DPB1等位基因频率进行统计分析。［结果］ （1）病例组分别检出3、10个低分辨等位基因型,对照组中分别检出3、9个低分辨等位基因型,HLA-DPA1、DPB1基因座位上等位基因频率分布均满足Hardy-Weninberg遗传平衡检验(P>0.05)。（2）维吾尔族HL患者中HLA-DPA1*03,DPB1*57,DPA1*01-DPB1*05,DPA1*01-DPB1*57,DPA1*02-DPB1*05,DPA1*02-DPB1*57,DPA1*03-DPB1*05 基因频率明显高于健康对照组,差异均有统计学意义（P<0.05）。［结论］ HLA-DPA1、DPB1基因与维吾尔族人群的HL发生密切相关。     

新疆维吾尔族霍奇金淋巴瘤HLA—A高分辨基因多态性分析

目的：研究人类白细胞抗原（humanleukocyteantigen,HLA—A）高分辨等位基因型与新疆地区维吾尔族霍奇金淋巴瘤（hodgkin’Slymphoma,HL）易感性的关系,以揭示遗传因素在HL发病中的作用。方法：采用病例一对照的研究设计和DNA测序分型（SBT）法,对45例维吾尔族HL患者和110名健康者进行HLA—A基因座位的精确分型,计算HLA_A基因座位等位基因的相对频率（RF）及基因频率（AF）。结果：1）病例组共检出33个高分辨等位基因型,对照组中共检出44个高分辨等位基因型,HLA-A基因座位上等位基因频率分布均满足Hardy-Weninberg遗传平衡检验,P=0．61。2）与新疆地区维吾尔族人群比较,维吾尔族HL患者中等位基因HLA-A＊01：01：01：01（45．48％＂US16．04％）、A＊03：01（39．68％VS18．35％）、A＊01：01（33．91％vs18．35％）、A＊02：07（28．18％VS13．73％）高分辨等位基因分布频率较高,差异有统计学意义,P〈0．01。HLA—A＊02：01（69．05％vs85．47％）和A＊1l：01（16．81％VS32．34％）则相对较低,差异有统计意义,P〈0．01。3）新疆地区维吾尔族HL患者与维吾尔族健康人抗原型均以A2最为多见,各型在病例组与对照组之间分布差异无统计学意义,P〉0．05。结论：HLA-A＊01：01：01：01、A＊03：01、A＊01：01和A＊02：07基因型与维吾尔族HL存在阳性关联,可能为维吾尔族HL发病的易感基因,而HLA-A＊02：01、A＊ll：01可能为维吾尔族HL发病的拮抗基因。     

新疆维吾尔族女性乳腺癌与HLA-DRB1基因多态性的关系及临床意义

目的:研究新疆维吾尔族女性乳腺癌的发生与人类白细胞抗原(HLA) DRB1等位基因多态性的关系,探讨乳腺癌的遗传易感性。方法:分别收集维吾尔族女性乳腺癌患者和健康人外周血标本196和230例,提取细胞基因组DNA,采用序列特异性引物聚合酶链反应(PCR- SSP)和毛细管电泳测序(CE)的方法进行HLA-DRB1基因多态性鉴定。结果：乳腺癌患者外周血DNA的HLA-DRB1*01多态性频率显著高于健康对照(χ²=10.180,OR=4.550,P<0.05),HLA-DRB1*16多态性低于对照(χ²=4.792,OR=0.492,P<0.05),而其他位点多态性两组间的差异无统计学意义(P>0.05)。结论:维吾尔族女性乳腺癌的发生可能与HLA-DRB1等位基因多态性存在密切关系,对于揭示乳腺癌发病机制及临床诊断提供了客观依据。     

南疆维吾尔族妇女宫颈癌与种族遗传易感性的关系研究

目的：探讨人类白细胞抗原HLA-DRB1基因多态性与南疆维吾尔族宫颈癌的关系。方法：采用聚合酶联反应序列特异性寡核苷酸探针（Polymerase chain reactiion sequence-specific olgonucleotide,PCR-SSO）法对200例南疆维吾尔族宫颈癌患者及200例正常妇女宫颈组织中检测HLA-DRBI的等位基因。结果：1）HLA-DRB1^＊。15在宫颈癌组中出现的频率明显高于对照组，并有统计学差异，OR〉1（χ^2=10．890，P=0．001．OR=2．061）2）HLA-DRB1^＊08在宫颈癌组中出现的频率明显低于对照组，并有统计学差异，OR〈1（χ^2=4．061，P=0．044，OR=0．463）。3）HLA-DRB1的其他等位基因在宫颈癌组及对照组中出现的频率无显著性差异（P〉0．05）。结论：HLA-DRB1^＊15可能与维吾尔族妇女对宫颈癌的遗传易感性有关，是维吾尔族妇女对宫颈癌的易感基因；可能是维吾尔族妇女宫颈癌患病率高的原因之一而HLA-DRB1^＊08可能为维吾尔族妇女宫颈癌的保护基因，维吾尔族妇女宫颈癌易感基因及保护基因的检测可能在高危人群的检测及群体遗传干预工作中有一定的指导意义。     

GSTP1基因多态性与新疆维、汉肺癌易感性的关系

目的探讨谷胱甘肽S转移酶P1基因（glutathione S-transferase P1,GSTP1）rs1695位点多态性与新疆地区维吾尔族（维族）和汉族肺癌患者的相关性。方法采用病例—对照研究方法,选取维族、汉族肺癌患者各80例作为病例组,另以维族、汉族健康人群各80例为对照组,运用限制性片段长度多态性聚合酶链反应（PCRrestriction fragment length polymorphism,PCR-RFLP）技术检测GSTP1基因Ile105Val多态性,分析其基因型频率在2个民族间分布的差异。结果 （1）GSTP1基因rs1695位点多态性在对照组与病例组中的分布均符合HardyWeinberg平衡;（2）在维族人群中,GSTP1基因rs1695位点基因型在病例组与对照组中的分布频率差异无统计学意义（P〉0.05）。在汉族人群中,携带G等位基因者发生肺癌的风险增加（OR=2.170,95%CI：1.146~4.107,P〈0.05）;（3）维族人群突变型杂合子AG和纯合子GG基因型频率均高于汉族,其中在对照组中维族GSTP1（GG）基因型频率较汉族高1.3倍（8.8%vs 3.8%）,但差异均无统计学意义（均P〉0.05）。结论 GSTP1基因rs1695多态性与汉族人群肺癌发病风险相关,与维吾尔族人群无关,其相关性具有民族差异。     

新疆地区宫颈癌HLA-DQB1等位基因与临床特征及近期疗效相关性研究

目的 分析新疆地区维吾尔族与汉族宫颈癌患者HLA-DQB1等位基因频率差异,探索HLA-DQB1与临床特征和近期疗效之间的关系.方法 纳入2013-05-1-2013-12-30新疆医科大学附属肿瘤医院收治的68例维吾尔族及20例汉族宫颈癌患者,采集外周血并分离提取DNA,检测HLA-DQB1基因.比较不同临床特征和近期疗效之间基因频率的差异.结果 维吾尔族HLA-DQB1* 03基因频率为33.1％,低于汉族的55.0％,差异有统计学意义,P＜0.05;维吾尔族HLA-DQB1*02基因频率为30.9％,高于汉族的10.0％,差异有统计学意义,P＜0.05.维吾尔族HLA-DQB1* 04、HLA-DQB1* 05和HLA-DQB1* 06等位基因频率分别为5.9％、8.8％和21.3％,汉族HLA-DQB1*04、HLA-DQB1*05和HLA-DQB1*06等位基因频率分别为5.0％、12.5％和17.5％,差异均无统计学意义,P＞0.05.HLA-DQB1各等位基因频率在不同年龄分组及HPV16表达分组之间比较,差异均无统计学意义,P＞0.05.治疗有效(CR+PR)患者HLA-DQB1*03基因频率为42.9％,高于治疗无效(SD+ PD)患者的26.0％,差异有统计学意义,P＜0.05.其余各等位基因频率在两组之间比较差异均无统计学意义,P＞0.05.结论 新疆地区维吾尔族宫颈癌患者HLA-DQB1* 03基因频率低于文献报道,HLA-DQB1* 02基因频率高于文献报道;HPV16阳性患者HLA DQB1* 04基因频率高于HPV16阴性患者;治疗有效患者HLA-DQB1* 03等位基因频率高于治疗无效患者;HLA-DQB1* 03等位基因可能与近期疗效有关.     

人类白细胞抗原-E基因多态性与乳腺癌遗传易感性的关系

目的 探讨人类白细胞抗原-E（HLA-E） 基因多态性与中国张家口地区汉族女性乳腺癌遗传易感性的关系。方法 采用聚合酶链反应-序列特异性引物（PCR-SSP）法对中国张家口地区200例乳腺癌患者和114例健康对照人群HLA-E等位基因进行检测。结果 乳腺癌患者和健康对照组均检出两种等位基因：HLA-E*0101和HLA-E*0103;共检出三种基因型：HLA-E*0101/ HLA-E*0101、HLA-E*0101/HLA-E*0103和HLA-E*0103/ HLA-E*0103。其中HLA-E*0103等位基因和HLA-E*0103/HLA-E*0103基因型在乳腺癌患者组的分布频率明显高于健康对照组,差异有统计学意义（P ＜0.01）。且携带HLA-E*0103/ HLA-E*0103基因型的个体乳腺癌发病风险明显增加（OR=2.05,P=0.004）。结论 HLA-E基因多态性与中国张家口地区汉族女性乳腺癌遗传易感性相关,并且HLA-E*0103/ HLA-E*0103等位基因可能是易感基因。     

NRG1基因多态性协同miRNA-142水平与甲状腺癌侵袭转移的关系研究

摘 要： ［目的］ 分析神经调节素1（NRG1）基因多态性协同微小核糖核酸miRNA-142（miR-142）水平与甲状腺癌侵袭转移的关系。［方法］ 选择120例甲状腺癌患者作为病例组,另选同期体检的120名健康者作为对照组。采用聚合酶链反应-限制性片段长度多态性法（PCR-RFLP）测定NRG1基因3个不同位点的单核苷酸多态性（SNP）,TaqMan等位基因分型技术分析基因分型及基因频率,实时定量PCR法测定血清miR-142水平。对比各组间NRG1基因多态性、miR-142水平差异,进行Logistic回归交互作用分析,绘制受试者工作特征（ROC）曲线,分析NRG1基因多态性协同miR-142水平预测甲状腺癌患者包膜浸润、淋巴结转移的价值。［结果］ 病例组NRG1基因rs6994992、rs7835688位点基因型分布频率与对照组比较,差异无统计学意义（P＞0.05）;病例组NRG1基因rs3924999位点携带A等位基因突变的基因型AA+GA与野生型GG相比,差异有统计学意义（P＜0.05）,携带AA+GA基因型的发病风险增加2.664倍（95%CI：1.062~6.684）;病例组NRG1基因rs3924999位点等位基因频率分布与对照组比较,差异有统计学意义（P＜0.05）,等位基因A突变可使发病风险增加2.056倍（95%CI：1.388~3.045）。病例组血清miR-142表达水平（0.61±0.19）低于对照组（1.00±0.21）（P＜0.05）。包膜浸润组、淋巴结转移组患者NRG1基因rs3924999位点基因频率分布分别与无包膜浸润组、无淋巴结转移组相比,差异均有统计学意义（P＜0.05）。Logistic回归交互分析证实NRG1基因rs3924999位点多态性、miR-142之间存在交互作用,NRG1基因rs3924999位点多态性协同miR-142水平预测甲状腺癌患者包膜浸润、淋巴结转移的AUC分别为0.785（95%CI：0.701~0.869）、0.797（95%CI：0.715~0.897）。［结论］ NRG1基因rs3924999位点多态性、miR-142水平与甲状腺癌发生、侵袭、转移密切相关,两者存在交互作用,且协同有助于预测甲状腺患者包膜浸润、淋巴结转移。     

HLA-DRB1*1501和DQB1*0602与新疆哈萨克族HPV 感染及食管癌发生的相关性研究*

目的:从基因水平探讨新疆哈萨克族食管鳞癌的HPV 16E6 感染及食管鳞癌发生与HLA-DRB1,DQB 1 等位基因的遗传易感性,为寻找哈萨克族食管鳞癌的易感基因提供参考。方法:采用聚合酶链反应（PCR ）技术检测200 例哈萨克族食管鳞癌和150 例哈族萨克正常人群HPV 16E6 基因的表达情况,运用序列特异性引物聚合酶链反应技术（PCR-SSP ）,检测新疆哈萨克族食管鳞癌患者200 例,哈萨克族正常人群食管膜膜150 例的HLA-DRB1*1501和HLA-DQB1*0602的分布。结果:新疆哈萨克族食管鳞癌患者HPV 16E6 感染率为41% ,明显高于哈萨克族正常人群感染率的14%（P<0.001,OR= 3.94）;HPV 16E6 感染与哈萨克族正常人群HLA-DRB1*1501,HLA-DQB1*0602的无相关性（P>0.05）;新疆哈萨克族食管鳞癌患者HLA-DRB1*1501和HLA-DQB1*0602基因分布频率显著高于哈萨克族正常人群（0.455:0.232,P<0.001,OR= 2.78;0.69比0.554,P=0.006,OR= 1.80）;HLA-DQB1*0602基因阳性率在中低分化鳞癌组中（68.8%）的分布高于高分化鳞癌组（31.2%）,差异有统计学意义（P<0.05）。 结论:HPV 16E6 的感染可能是新疆哈萨克族食管癌发生的重要因素之一。HLA-DRB1*1501和HLA-DQB1*0602是哈萨克族食管鳞癌的易感基因,其中HLA-DQB1*0602与哈萨克族食管鳞癌的分化程度有关。      

肿瘤坏死因子基因多态性与湖北汉族人群非霍奇金淋巴瘤发病的相关性

目的：研究我国湖北汉族人群TNF的基因多态性与非霍奇金淋巴瘤（NHL）发病的关系。方法：采用病例对照研究和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测160例NHL患者和214例健康对照者中TNFα-308、LTα-252基因型分布。结果：NHL组与健康对照组TNFα-308基因型、等位基因频率总体分布差异无统计学意义（P均〉0.05）;NHL组与健康对照组相比LTα-252 AA基因型频率相比明显减低,差异有统计学意义（19%比29%,χ2=4.513,P=0.034,OR=1.697,95%CI：1.039-2.773）,而LTα-252 GG、AG基因型及等位基因频率总体分布差异无统计学意义（P均〉0.05）;TNFα-308、LTα-252基因型与NHL患者的病理类型、临床分期及进展无明显相关性（P均〉0.05）。结论：LTα-252位点基因型与湖北汉族人群NHL发病有相关性。     

The investigation of HLA microsatellites influence in predisposition to sarcoidosis among Croatians

The aim of the present study was to analyze the distribution of HLA alleles (A, B, DRB1, DQB1) and HLA microsatellite alleles (TNFa, TNFb, TNFd, D6S273, D6S1014) in the Croatian patients with acute (N=93), as well as chronic sarcoidosis (N=40), in comparison to healthy controls (N=177), and investigate whether the polymorphism within the HLA region could be associated with different forms of sarcoidosis. Genomic DNA was isolated from peripheral blood. Patients were analyzed for HLA class I loci (A, B) by serology, while PCR-SSP method was used for HLA class II loci (DRB1, DQB1). Five HLA microsatellites were analyzed by PCR and electrophoresis in an automated sequencer. No significant deviation in the distribution of frequencies at HLA class I alleles was observed between the two patients' subgroups and controls. Regarding the HLA class II alleles, a statistically significant increase in frequency of HLA-DRB1*03 and DQB1*0201 allele was found among patients with acute sarcoidosis in comparison to controls as well as in comparison to patients with chronic sarcoidosis. The same finding was observed for HLA-DRB1*03/DQB1*0201 haplotype (Pcorr=0.0168; OR=2.83). In the group of patients with chronic sarcoidosis DRB1*11 (P=0.0219; OR=2.44), DRB1*15 (P=0.0414; OR=2.47) demonstrated statistically significant difference in comparison to controls only, while a lower frequency of DRB1*13 (P=0.0156; OR=0.24) in this group was statistically significant when compared to both patients with acute sarcoidosis and controls. None of the alleles at TNFa microsatellite showed significant difference in distribution among both subgroups of patients and controls. Significant difference between patients with acute form of disease and controls was found for the following alleles: TNFd-2 (Pcorr=0.00007; OR=4.89), D6S273-7 (Pcorr=0.0213; OR=2.96), and D6S1014-7 (Pcorr=0.0028; OR=3.97). On the other hand, patients with chronic sarcoidosis differed from control subjects for D6S1014-8 (Pcorr=0.0296; OR=8.35) allele. This study suggests the existence of an association of non-HLA markers with sarcoidosis and the involvement of the region between HLA-DQB1 and D6S273 loci in its pathophysiology.     

HLA-DRB1,-DQA1 and -DQB1 Allele and Haplotype Frequencies in Female Patients with Early Onset Breast Cancer

Based on the reports, few HLA class II alleles are associated with susceptibility or protection in breast cancer. Here we investigate the association between HLA class II alleles and breast cancer in Iranian women. 100 patients with pathologically proven breast cancer who referred to Cancer Institute were randomly selected and compared with a group of 80 healthy blood donor subjects. The patients were studied in two groups, group 1 includes patients aging 40?years or younger and group 2 include patients aging over 40?years. HLA class II alleles were determined by amplification of DNA followed by HLA-typing using sequence-specific primer (SSP) for each allele. In group 1, the most frequent alleles were HLA-DQA1*0301 (P?=?0.002, OR?=?3.3) and HLA-DQB1*0302 (P?=?0.04, OR?=?2.8). In group 2, the following alleles increased significantly than those in controls including HLA-DQA1*0301 (P?=?0.001, OR?=?3.4) and HLA-DRB1*0301 (P?=?0.04, OR?=?2.3). In complete group of patients, the frequency of HLA-DQA1*0301 (P?=?0.001, OR?=?3.4) and HLA-DRB1*1303 (P?=?0.02, OR?=?2.3) increased significantly than those in control group. HLA-DQA1*0505, HLA-DQA1*0101, HLA-DRB1*1301and HLA-DRB1*0101 alleles showed negative association with breast cancer. Our findings suggest that HLA-DQA1*0301 allele is mainly associated with increased risk of breast cancer including early-onset of the disease. HLA-DQA1*0505 and HLA-DRB1*1301 are involved in protection. We conclude that specific alleles of HLA class II influence breast cancer risk.     

Association of HLA class II allele and haplotype frequencies with chronic myelogenous leukemia and age-at-onset of the disease

Chronic myelogenous leukemia (CML) is characterized by the presence of Philadelphia chromosome resulting from bcr/abl translocation. To clarify the association between HLA class II allele and haplotype frequencies in CML, 50 patients referred to Hematology Oncology and Bone Marrow Transplantation (BMT) center, Shariaty Hospital, Tehran, Iran, were randomly selected and compared with a group of 80 unrelated healthy blood donor subjects. HLA class II alleles were determined by PCR-SSP method. The results showed that the frequencies of DQB1*03011 (P=0.01) and DQA1*0505 (P=0.05) were higher, while that of DQB1*03032 (P=0.04) was lower in patients than in the controls. Regarding age-at-onset, the frequency of HLA-DRB1*07 (P=0.03) and -DQA1*0201 (P=0.03) alleles were higher in patients younger than 35 years. The most frequent haplotypes in our CML patients were HLA-DRB1*11/-DQB1*03011/-DQA1*0505 (P=0.01) and HLA-DRB1*04/-DQB1*0302/-DQA1*03011 (P=0.02). In conclusion, it is suggested that positive and negative association in certain HLA alleles and haplotypes exist in Iranian patients with CML.     

Effects of cytochrome P450 1A1 and uridine-diphosphate-glucuronosyltransferase 1A1 allelic polymorphisms on the risk of development and the prognosis of head and neck cancers

We studied the effect of allelic polymorphisms of cytochrome P450 1A1 (CYP1A1) and uridine-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) on the risk of development of head and neck cancers and overall survival. One hundred and forty-two head and neck cancer patients (48 with laryngeal, 42 with hypopharyngeal and 52 with mesopharyngeal tumours) were included in the study. The control group (150 individuals) included volunteers without malignant tumours. There was no statistically significant difference in age, sex distribution, or smoking habits between the two groups. The participants were genotyped for the CYP1A1 isoleucine/valine (Ile/Val) polymorphism in exon 7 and for the UGT1A1 thymine-adenine-repeat polymorphism (*1 and *28 alleles) in the promoter region of the gene. The effect of the allelic variants on survival was studied using the log-rank test, whereas the χ-test and odds ratios (OR) with 95% confidence intervals (CI) were used to compare the allelic frequencies between patients and controls. Our study revealed a significant link between the occurrence of the CYP1A1 Ile/Val, Val/Val (OR: 1.72, 95% CI: 1.02-2.96, P=0.044) and UGT1A1*28 alleles (OR: 2.74, 95% CI: 1.45-5.18, P=0.002) and an increased risk of head and neck cancers. These alleles decreased the duration of survival significantly (P=0.018 and 0.006). The survival was significantly more strongly reduced when the two high-risk alleles were carried simultaneously (OR: 2.149, 95% CI: 1.111-4.157, P=0.001). Our results suggest that the use of the CYP1A1 Ile/Val and Val/Val variants and UGT1A1*28 as biomarkers can aid risk assessment while their prognostic value can aid planning of individual therapy.     

Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women

BACKGROUND: Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. METHODS: The authors evaluated common polymorphisms in the CYP1A1 gene in relation to breast carcinoma risk in a large population-based case-control study among Chinese women, the Shanghai Breast Cancer Study. Because the CYP1A1*3 and CYP1A1*4 alleles were not detected in the study population, analyses were performed for CYP1A1*2A (T-->C transition in the 3' noncoding region) and CYP1A1*2C (A-->G transition in exon 7, resulting in a substitution of Val for Ile) in 1134 patients with breast carcinoma and 1227 controls. RESULTS: The frequencies of the variant allele were 38.3% and 38.8% among cases and controls (P = 0.91), respectively, for the CYP1A1*2A polymorphism, and 23.1% and 24.8% (P = 0.26) for the CYP1A1*2C polymorphism. Homozygosity for both variant alleles in these 2 polymorphic sites (CYP1A1*2B) was associated with a borderline significant odds ratio (OR) of 0.71 (95% confidence interval [CI], 0.47-1.06). The reduced risk was more pronounced among postmenopausal women with long duration (> 30 yrs) of menstruation (OR = 0.43; 95% CI, 0.19-0.99) or among women with a low waist-to-hip ratio (OR = 0.52; 95% CI, 0.28-0.94). CONCLUSIONS: Results from the current study suggest that homozygosity for the CYP1A1*2A and CYP1A1*2C alleles in the CYP1A1 gene may be associated with a reduced risk for breast carcinoma, particularly among lean women with long-term endogenous estrogen exposure.     

Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India

Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions 9 and 37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.     

HLA and MICA associations with head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a very aggressive tumour arising from the epithelial lining of the upper aerodigestive tract. The precise mechanisms involved in the pathogenesis of HNSCC have not been elucidated. Previous studies observed aberrant HLA expression patterns on HNSCC tumour cells and this study focused on the allelic polymorphism of HLA genes and the MHC class I chain related gene A (MICA) and HNSCC. We investigated whether associations with HLA and/or MIC alleles or haplotypes are involved in the pathogenesis of HNSCC and could explain the observed HLA expression patterns. Patients and controls were typed for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 with sequence specific priming (SSP), supplemented with sequencing based typing (SBT). MICA allelic polymorphism was included and MICA allele assignment was based upon the combination of high resolution SBT of exons 2-4 in combination with repeat analysis and nucleotide polymorphism of exon 5. HLA-B *35 (p=0.014, OR=0.31) and HLA-B *40 (p=0.013, OR=2.9) were significantly associated in respectively the metastasized patients and the oral cavity patients. In addition, the HLA-B *40-DRB1 *13 haplotype (p=0.016, OR=4.1) was more often observed in the oral cavity patient group. The biological significance of the prevalence of specific HLA haplotypes in patients with oral cavity HNSCC and metastasizing HNSCC requires further investigation.     

中国南方汉族急性淋巴细胞白血病患者572例的HLA基因和单倍型分析

 目的　研究HLA-A、B、DRB1基因和单倍型与中国南方汉族急性淋巴细胞白血病（ALL）的疾病相关性。方法　应用最大似然性方法分别计算南方汉族ALL患者组572例和5645名南方汉族健康供者HLA-A、B、DRB1基因和单倍型频率,采用χ2检验方法比较其分布差异。结果　ALL组HLA-A33、B58和DRB1*17基因频率均低于对照组[HLA-A33（7.15 %比9.3 %,OR＝0.73,P＜0.05）、B58（5.93 %比8.75 %,OR＝0.64,P＜0.05）和DRB1*17（5.15%比6.30 %,OR＝0.82,P＜0.05）];A3、B51和DRB*12基因频率均高于对照组[A3（2.1 %比1.26 %,OR＝1.7,P＜0.05）,B51（7. 25 %比5.78 %,OR＝1.3,P＜0.05）和DRB*12（16.13 %比12.99 %,OR＝1.35,P＜0.05）];HLA-A33-B58-DRB1*17单倍型频率低于对照组（2.46 %比4.14 %,OR＝0.35,P＜0.05）,A2-B51- DRB1*12单倍型频率高于对照组（1.24 %比0.89 %,OR＝1.66,P＜0.05）。结论　携带有A33-B58-DRB1*17单倍型个体可能与降低ALL的发病风险有相关性,A3基因和A2-B51- DRB1*12可能与增加ALL发病风险有弱相关性。